Mucosal lymphocytes from AIDS patients severely depressed systemic immunity still secrete large amounts of IFN-γ and IL-4 in the intestinal mucosa

1997 ◽  
Vol 56 (1-3) ◽  
pp. 181
Author(s):  
M Carol
1997 ◽  
Vol 56 ◽  
pp. 181
Author(s):  
M. Carol ◽  
A. Lambrechts ◽  
S. Evrard ◽  
M. Libin ◽  
D. Urbain ◽  
...  

Gut ◽  
1998 ◽  
Vol 42 (5) ◽  
pp. 643-649 ◽  
Author(s):  
M Carol ◽  
A Lambrechts ◽  
A Van Gossum ◽  
M Libin ◽  
M Goldman ◽  
...  

Background—Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses.Aims—To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation.Patients—Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa.Methods—Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT).Results—The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4.Conclusions—Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.


2000 ◽  
Vol 68 (1) ◽  
pp. 197-204 ◽  
Author(s):  
Daniel F. Hoft ◽  
Anita R. Schnapp ◽  
Christopher S. Eickhoff ◽  
Stanford T. Roodman

ABSTRACT In general, gamma interferon (IFN-γ)-producing CD4+Th1 cells are important for the immunological control of intracellular pathogens. We previously demonstrated an association between parasite-specific induction of IFN-γ responses and resistance to the intracellular protozoan Trypanosoma cruzi. To investigate a potential causal relationship between Th1 responses andT. cruzi resistance, we studied the ability of Th1 cells to protect susceptible BALB/c mice against virulent parasite challenges. We developed immunization protocols capable of inducing polarized Th1 and Th2 responses in vivo. Induction of parasite-specific Th1 responses, but not Th2 responses, protected BALB/c mice against virulent T. cruzi challenges. We generated T. cruzi-specific CD4+ Th1 and Th2 cell lines from BALB/c mice that were activated by infected macrophages to produce their corresponding cytokine response profiles. Th1 cells, but not Th2 cells, induced nitric oxide production and inhibited intracellular parasite replication in T. cruzi-infected macrophages. Despite the ability to inhibit parasite replication in vitro, Th1 cells alone could not adoptively transfer protection againstT. cruzi to SCID mice. In addition, despite the fact that the adoptive transfer of CD4+ T lymphocytes was shown to be necessary for the development of immunity protective against primary T. cruzi infection in our SCID mouse model, protective secondary effector functions could be transferred to SCID mice from memory-immune BALB/c mice in the absence of CD4+ T lymphocytes. These results indicate that, although CD4+ Th1 cells can directly inhibit intracellular parasite replication, a more important role for these cells in T. cruzi systemic immunity may be to provide helper activity for the development of other effector functions protective in vivo.


2021 ◽  
Vol 8 ◽  
Author(s):  
Qingsong Tang ◽  
Hongbo Yi ◽  
Weibin Hong ◽  
Qiwen Wu ◽  
Xuefen Yang ◽  
...  

Lactobacillus plantarum CGMCC 1258 and Lactobacillus reuteri LR1 are two important strains of probiotics. However, their different advantages in the probiotic effect of weaned pigs are still poorly understood. Therefore, the study was to investigate the comparative effects of dietary supplementation of L. plantarum CGMCC 1258 and L. reuteri LR1 on growth performance, antioxidant function, and intestinal immunity in weaned pigs. Ninety barrows [initial body weight (BW) = 6.10 ± 0.1 kg] 21 days old were randomly divided into 3 treatments with 5 replicates, each replicate containing 6 pigs. Pigs in control (CON) were fed a basal diet, and the basal diets supplemented with 5 × 1010 CFU/kg L. plantarum CGMCC 1258 (LP) or L. reuteri LR1 (LR) for 42 days, respectively. The results showed that LP increased (p < 0.05) serum superoxide dismutase (SOD), and decreased (p < 0.05) serum malondialdehyde (MDA) and the expression and secretion of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in intestinal mucosa, but has no significant effect on growth performance and diarrheal incidence. However, LR increased (p < 0.05) final BW and average daily gain (ADG), reduced (p < 0.05) 29–42-day diarrheal incidence, decreased (p < 0.05) the expression and secretion of IL-1β, IL-6, TNF-α, and IFN-γ, and increased (p < 0.05) the expression of transforming growth factor-β (TGF-β) in intestinal mucosa. In addition, the serum glutathione peroxidase (GSH-PX), mRNA relative expression of Na+-K+-2Cl– co-transporter 1 (NKCC1) and cystic fibrosis transmembrane conductance regulator (CFTR) and the content of toll-like relative (TLR2) and TLR4 in the jejunum, and secretory immunoglobulin (sIgA) content of ileal mucosa were higher (p < 0.05) than LP. Collectively, dietary L. plantarum CGMCC 1258 improved intestinal morphology, intestinal permeability, intestinal immunity, and antioxidant function in weaned pigs. Dietary L. reuteri LR1 showed better growth performance, a lower incidence of diarrhea, better intestinal morphology, and a higher extent of immune activation in weaned pigs.


1999 ◽  
Vol 276 (3) ◽  
pp. G599-G605 ◽  
Author(s):  
Maria T. Abreu-Martin ◽  
Andrew A. Palladino ◽  
Mary Faris ◽  
Nelson M. Carramanzana ◽  
André E. Nel ◽  
...  

Fas is expressed constitutively by colonic epithelial cells, and its ligand is expressed by intraepithelial and lamina propria lymphocytes. Fas ligation induces apoptosis in colonic epithelial cells and is implicated in the epithelial damage seen in ulcerative colitis. To understand the pleiotropic effects of Fas in the intestinal mucosa, we have examined signaling pathways activated by Fas in HT-29 colonic epithelial cells. HT-29 cells were stimulated with anti-Fas in the presence or absence of interferon-γ (IFN-γ). Activation of mitogen-activated protein kinase pathways was assessed by kinase assay, Western blots, and promoter-reporter assays. Electromobility shift assays were used to assess activator protein-1 (AP-1) binding activity. IFN-γ increases expression of Fas on HT-29 cells. Signaling via Fas receptor, as determined by induction of c-Jun NH2-terminal kinase (JNK) activity and transcriptional activation of AP-1, is enhanced in IFN-γ-primed cells. Dominant-interfering mutants of the JNK pathway do not block Fas-mediated apoptosis. Signaling through Fas results in activation of JNK and AP-1 binding activity that is increased in the presence of IFN-γ. Inhibition of JNK does not block Fas-mediated apoptosis in these cells. Fas-Fas ligand interactions in the intestinal mucosa may lead to complex signal transduction cascades and gene regulation that culminate in apoptosis, cytokine secretion, or other novel functions.


1995 ◽  
Vol 108 (4) ◽  
pp. A781 ◽  
Author(s):  
Y Benhamou ◽  
N Kapel ◽  
M Gentilini ◽  
JG Gobert ◽  
P Opolon
Keyword(s):  

mBio ◽  
2021 ◽  
Author(s):  
Ai-Yu Gong ◽  
Yang Wang ◽  
Min Li ◽  
Xin-Tian Zhang ◽  
Silu Deng ◽  
...  

Epithelial cells along the mucosal surface provide the front line of defense against luminal pathogen infection in the gastrointestinal tract. These epithelial cells represent an integral component of a highly regulated communication network that can transmit essential signals to cells in the underlying intestinal mucosa that, in turn, serve as targets of mucosal immune mediators.


2004 ◽  
Vol 24 (14) ◽  
pp. 6298-6310 ◽  
Author(s):  
Shigeru Oshima ◽  
Tetsuya Nakamura ◽  
Shin Namiki ◽  
Eriko Okada ◽  
Kiichiro Tsuchiya ◽  
...  

ABSTRACT Intestinal epithelial cell-derived interleukin (IL)-7 functions as a pleiotropic and nonredundant cytokine in the human intestinal mucosa; however, the molecular basis of its production has remained totally unknown. We here showed that human intestinal epithelial cells both constitutively and when induced by gamma interferon (IFN-γ) produced IL-7, while several other factors we tested had no effect. Transcriptional regulation via an IFN regulatory factor element (IRF-E) on the 5′ flanking region, which lacks canonical core promoter sequences, was pivotal for both modes of IL-7 expression. IRF-1 and IRF-2, the latter of which is generally known as a transcriptional repressor, were shown to interact with IRF-E and transactivate IL-7 gene expression in an IFN-γ-inducible and constitutive manner, respectively. Indeed, tetracycline-inducible expression experiments revealed that both of these IRF proteins up-regulated IL-7 protein production, and their exclusive roles were further confirmed by small interfering RNA-mediated gene silencing systems. Moreover, these IRFs displayed distinct properties concerning the profile of IL-7 transcripts upon activation and expression patterns within human colonic epithelial tissues. These results suggest that the functional interplay between IRF-1 and IRF-2 serves as an elaborate and cooperative mechanism for timely as well as continuous regulation of IL-7 production that is essential for local immune regulation within human intestinal mucosa.


2018 ◽  
Vol 9 (5) ◽  
pp. 743-754 ◽  
Author(s):  
W. Du ◽  
H. Xu ◽  
X. Mei ◽  
X. Cao ◽  
L. Gong ◽  
...  

Bacillus is widely used in the livestock industry. This study was designed to evaluate the effects of probiotic Bacillus amyloliquefaciens SC06 (Ba), originally isolated from soil, in piglets diet as an alternative to antibiotics (aureomycin), mainly on intestinal epithelial barrier and immune function. Ninety piglets were divided into three groups: G1 (containing 150 mg/kg aureomycin in the diet); G2 (containing 75 mg/kg aureomycin and 1×108 cfu/kg Ba in the diet); G3 (containing 2×108 cfu/kg Ba in the diet without any antibiotics). The results showed that, compared with the antibiotic group (G1), villus length, crypt depth and villus length/crypt depth ratio of intestine significantly increased in the G2 and G3 groups. In addition, intestinal villi morphology, goblet-cell number, mitochondria structure and tight junction proteins of intestinal epithelial cells in G2 and G3 were better than in G1. The relative gene expression of intestinal mucosal defensin-1, claudin3, claudin4, and human mucin-1 in G3 was significantly lower, while the expression of villin was significantly higher than in the antibiotic group. Probiotic Ba could significantly decrease serum interferon (IFN)-α, IFN-γ, interleukin (IL)-1β, and IL-4 levels, whereas increase tumour necrosis factor (TNF)-α and IL-6 secretion. Ba could also significantly decrease cytokines TNF-α, IFN-γ, IL-1β, and IL-4 level in liver, whereas it significantly increased IFN-α. Furthermore, replacing antibiotics with Ba also significantly down-regulated gene expression of TNF and IL-1α in intestinal mucosa, but up-regulated IL-6 and IL-8 transcription. Dietary addition of Ba could significantly reduce the gene expression of nuclear factor kappa beta (NFκB)-p50 and Toll-like receptor (TLR)6, while there was no significant difference for that of myeloid differentiation primary response 88, TNF receptor-associated factor-6, nucleotide-binding oligomerisation domain-containing protein 1, TLR2, TLR4, and TLR9. Taken together, our findings demonstrated that probiotic Ba could increase the intestinal epithelial cell barrier and immune function by improving intestinal mucosa structure, tight junctions and by activating the TLRs signalling pathway.


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